Major Objectives: 1) Muscle. a) To understand the chemical basis and controls of the microcontractions at the actomyosin cross-bridges. b) To understand the contractile mechanism of vertebrate smooth muscle. 2) Circulation. To understand the diffusional component of tissue-capillary transport, and the normal controls of precapillary sphincter muscles. Methods: 1) Muscle. a) Shortening and concomitant ATP splitting are measured as myofibrils 1 sarcomere wide contract from normal or overextended initial length. Contraction at the theoretical minimum load, and therefore at the theoretical maximum velocity, is measured, as well as shortening under internal load. Effects of temperature, pCa, pMg, substrate, regulatory proteins, epinephrine, and propranolol on mechanochemical coupling are observed. b) The regularity of thin filament spacing is measured in gizzard smooth muscle to ascertain whether thick filaments of myosin do or do not exist in the thin filament lattice. 2) Circulation. Direct in vivo microscopy is used to measure diffusion distances in beating rat heart in situ as paO2 and paCO2 are varied. Similar methods are used to measure diffusion distances, uniformity of capillary distribution in 3 dimensions, and the number and arrangement of counter-current capillaries in rat gracilis muscle at rest and during contraction.